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Muscle Stem Cells (muscle + stem_cell)
Selected AbstractsAge Dependence of the Human Skeletal Muscle Stem Cell in Forming Muscle TissueARTIFICIAL ORGANS, Issue 3 2006Ralf Schäfer Abstract:, Human skeletal muscle stem cells from healthy donors aged 2,82 years (n = 13) and from three children suffering from Duchenne Muscular Dystrophy (DMD) were implanted into soleus muscles of immunoincompetent mice and were also expanded in vitro until senescence. Growth of implanted cells was quantified by structural features and by the amount of human DNA present in a muscle. Proliferative capacity in vitro and in vivo was inversely related to age of the donor. In vitro, a decline of about two mean population doublings (MPDs) per 10 years of donor's age was observed. Muscle stem cells from DMD children were prematurely aged. In general, cell preparations with low or decreasing content in desmin-positive cells produced more MPDs than age-matched high-desmin preparations and upon implantation more human DNA and more nonmyogenic than myogenic tissue. Thus, a "Desmin Factor" was derived which predicts "quality" of the human muscle tissue growing in vivo. This factor may serve as a prognostic tool. [source] Muscle stem cells and model systems for their investigationDEVELOPMENTAL DYNAMICS, Issue 12 2007Nicolas Figeac Abstract Stem cells are characterized by their clonal ability both to generate differentiated progeny and to undergo self-renewal. Studies of adult mammalian organs have revealed stem cells in practically every tissue. In the adult skeletal muscle, satellite cells are the primary muscle stem cells, responsible for postnatal muscle growth, hypertrophy, and regeneration. In the past decade, several molecular markers have been found that identify satellite cells in quiescent and activated states. However, despite their prime importance, surprisingly little is known about the biology of satellite cells, as their analysis was for a long time hampered by a lack of genetically amenable experimental models where their properties can be dissected. Here, we review how the embryonic origin of satellite cells was discovered using chick and mouse model systems and discuss how cells from other sources can contribute to muscle regeneration. We present evidence for evolutionarily conserved properties of muscle stem cells and their identification in lower vertebrates and in the fruit fly. In Drosophila, muscle stem cells called adult muscle precursors (AMP) can be identified in embryos and in larvae by persistent expression of a myogenic basic helix,loop,helix factor Twist. AMP cells play a crucial role in the Drosophila life cycle, allowing de novo formation and regeneration of adult musculature during metamorphosis. Based on the premise that AMPs represent satellite-like cells of the fruit fly, important insight into the biology of vertebrate muscle stem cells can be gained from genetic analysis in Drosophila. Developmental Dynamics 236:3332,3342, 2007. © 2007 Wiley-Liss, Inc. [source] Age Dependence of the Human Skeletal Muscle Stem Cell in Forming Muscle TissueARTIFICIAL ORGANS, Issue 3 2006Ralf Schäfer Abstract:, Human skeletal muscle stem cells from healthy donors aged 2,82 years (n = 13) and from three children suffering from Duchenne Muscular Dystrophy (DMD) were implanted into soleus muscles of immunoincompetent mice and were also expanded in vitro until senescence. Growth of implanted cells was quantified by structural features and by the amount of human DNA present in a muscle. Proliferative capacity in vitro and in vivo was inversely related to age of the donor. In vitro, a decline of about two mean population doublings (MPDs) per 10 years of donor's age was observed. Muscle stem cells from DMD children were prematurely aged. In general, cell preparations with low or decreasing content in desmin-positive cells produced more MPDs than age-matched high-desmin preparations and upon implantation more human DNA and more nonmyogenic than myogenic tissue. Thus, a "Desmin Factor" was derived which predicts "quality" of the human muscle tissue growing in vivo. This factor may serve as a prognostic tool. [source] Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx,THE LARYNGOSCOPE, Issue 7 2008Stacey L. Halum MD Abstract Objective: Current treatments for vocal fold paralysis are suboptimal in that they fail to restore dynamic function. Autologous muscle stem cell (MSC) therapy is a promising potential therapy for vocal fold paralysis in that it can attenuate denervation-induced muscle atrophy and provide a vehicle for delivery of neurotrophic factors, thereby potentially selectively guiding reinnervation. The goal of this project was to characterize optimal conditions for injected autologous MSC survival in the thyroarytenoid (TA) muscle following recurrent laryngeal nerve (RLN) injury by local administration of adjuvant factors. Study Design: Animal experiment. Methods: Unilateral RLN transection and sternocleidomastoid muscle (,1 g) biopsies were performed in 20 male Wistar rats. One month later, 106 autologous MSCs labeled via retroviral-enhanced green fluorescent protein (EGFP) transduction were injected into the denervated hemilarynx of each animal with one of four adjuvant therapies: cardiotoxin [(CTX) 10,5 M], insulin-like growth factor-1 [(IGF- 1) 100 ,g/mL], ciliary neurotrophic factor [(CNTF) 50 ,g/mL], or saline. Animals were euthanized 1 month later and larynges harvested, sectioned, and analyzed for MSC survival. Results: All specimens demonstrate extensive MSC survival, with fusion of the MSCs with the denervated myofibers. Based on mean fluorescent intensity of the laryngeal specimens, IGF-1 and CNTF had the greatest positive influence on MSC survival. Myofiber diameters demonstrated myofiber atrophy to be inversely related to MSC survival, with the least atrophy in the groups having the greatest MSC survival. Conclusions: Autologous MSC therapy may be a future treatment for vocal fold paralysis. These findings support a model whereby MSCs genetically engineered to secrete CNTF and/or IGF-1 may not only promote neural regeneration, but also enhance MSC survival in an autocrine fashion. [source] Analysis of human muscle stem cells reveals a differentiation-resistant progenitor cell population expressing Pax7 capable of self-renewalDEVELOPMENTAL DYNAMICS, Issue 1 2009Bradley Pawlikowski Abstract Studies using mouse models have established a critical role for resident satellite stem cells in skeletal muscle development and regeneration, but little is known about this paradigm in human muscle. Here, using human muscle stem cells, we address their lineage progression, differentiation, migration, and self-renewal. Isolated human satellite cells expressed ,7-integrin and other definitive muscle markers, were highly motile on laminin substrates and could undergo efficient myotube differentiation and myofibrillogenesis. However, only a subpopulation of the myoblasts expressed Pax7 and displayed a variable lineage progression as measured by desmin and MyoD expression. Analysis identified a differentiation-resistant progenitor cell population that was Pax7+/desmin, and capable of self-renewal. This study extends our understanding of the role of Pax7 in regulating human satellite stem cell differentiation and self-renewal. Developmental Dynamics 238:138,149, 2009. © 2008 Wiley-Liss, Inc. [source] Muscle stem cells and model systems for their investigationDEVELOPMENTAL DYNAMICS, Issue 12 2007Nicolas Figeac Abstract Stem cells are characterized by their clonal ability both to generate differentiated progeny and to undergo self-renewal. Studies of adult mammalian organs have revealed stem cells in practically every tissue. In the adult skeletal muscle, satellite cells are the primary muscle stem cells, responsible for postnatal muscle growth, hypertrophy, and regeneration. In the past decade, several molecular markers have been found that identify satellite cells in quiescent and activated states. However, despite their prime importance, surprisingly little is known about the biology of satellite cells, as their analysis was for a long time hampered by a lack of genetically amenable experimental models where their properties can be dissected. Here, we review how the embryonic origin of satellite cells was discovered using chick and mouse model systems and discuss how cells from other sources can contribute to muscle regeneration. We present evidence for evolutionarily conserved properties of muscle stem cells and their identification in lower vertebrates and in the fruit fly. In Drosophila, muscle stem cells called adult muscle precursors (AMP) can be identified in embryos and in larvae by persistent expression of a myogenic basic helix,loop,helix factor Twist. AMP cells play a crucial role in the Drosophila life cycle, allowing de novo formation and regeneration of adult musculature during metamorphosis. Based on the premise that AMPs represent satellite-like cells of the fruit fly, important insight into the biology of vertebrate muscle stem cells can be gained from genetic analysis in Drosophila. Developmental Dynamics 236:3332,3342, 2007. © 2007 Wiley-Liss, Inc. [source] Signal modelization for improved precision of assessment of minimum and mean telomere lengthsELECTROPHORESIS, Issue 2 2008Elodie Ponsot Dr. Abstract Telomere length is an important measure of cell and tissue regenerative capacities. The mean telomere length is classically used as global indicator of a tissue telomere length. In skeletal muscle, which is made of postmitotic myonuclei and satellite cells (muscle stem cells), minimum telomere length is also used to assess the telomere length of satellite cells and newly incorporated myonuclei. At present, the estimation of the method reproducibility during the assessment of mean and minimum telomere length using Southern blot analysis has never been documented. The aim of this report is to describe a signal modelization for improved precision of assessment of minimum and mean telomere lengths and to document the method reproducibility. Telomeres are assessed using a Southern technique where the gel is directly hybridized with the specific probe without the membrane-transferring step in order to prevent telomeric low signal loss. We found that the improved signal analysis for determination of telomere length is associated with coefficients of variation ranging from 1.37 to 4.29% for the mean telomeric restriction fragment (TRF) length and from 2.04 to 4.95% for the minimum TRF length. Improved method reproducibility would allow saving time and biological material as duplicate and triplicate measurement of the same sample is no longer required. [source] Age Dependence of the Human Skeletal Muscle Stem Cell in Forming Muscle TissueARTIFICIAL ORGANS, Issue 3 2006Ralf Schäfer Abstract:, Human skeletal muscle stem cells from healthy donors aged 2,82 years (n = 13) and from three children suffering from Duchenne Muscular Dystrophy (DMD) were implanted into soleus muscles of immunoincompetent mice and were also expanded in vitro until senescence. Growth of implanted cells was quantified by structural features and by the amount of human DNA present in a muscle. Proliferative capacity in vitro and in vivo was inversely related to age of the donor. In vitro, a decline of about two mean population doublings (MPDs) per 10 years of donor's age was observed. Muscle stem cells from DMD children were prematurely aged. In general, cell preparations with low or decreasing content in desmin-positive cells produced more MPDs than age-matched high-desmin preparations and upon implantation more human DNA and more nonmyogenic than myogenic tissue. Thus, a "Desmin Factor" was derived which predicts "quality" of the human muscle tissue growing in vivo. This factor may serve as a prognostic tool. [source] Differentiation rather than aging of muscle stem cells abolishes their telomerase activityBIOTECHNOLOGY PROGRESS, Issue 4 2009Matthew S. O'Connor Abstract A general feature of stem cells is the ability to routinely proliferate to build, maintain, and repair organ systems. Accordingly, embryonic and germline, as well as some adult stem cells, produce the telomerase enzyme at various levels of expression. Our results show that, while muscle is a largely postmitotic tissue, the muscle stem cells (satellite cells) that maintain this biological system throughout adult life do indeed display robust telomerase activity. Conversely, primary myoblasts (the immediate progeny of satellite cells) quickly and dramatically downregulate telomerase activity. This work thus suggests that satellite cells, and early transient myoblasts, may be more promising therapeutic candidates for regenerative medicine than traditionally utilized myoblast cultures. Muscle atrophy accompanies human aging, and satellite cells endogenous to aged muscle can be triggered to regenerate old tissue by exogenous molecular cues. Therefore, we also examined whether these aged muscle stem cells would produce tissue that is "young" with respect to telomere maintenance. Interestingly, this work shows that the telomerase activity in muscle stem cells is largely retained into old age wintin inbred "long" telomere mice and in wild-derived short telomere mouse strains, and that age-specific telomere shortening is undetectable in the old differentiated muscle fibers of either strain. Summarily, this work establishes that young and old muscle stem cells, but not necessarily their progeny, myoblasts, are likely to produce tissue with normal telomere maintenance when used in molecular and regenerative medicine approaches for tissue repair. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] A tissue-engineered suburethral sling in an animal model of stress urinary incontinenceBJU INTERNATIONAL, Issue 4 2005Tracy W. Cannon OBJECTIVE To create and evaluate the functional effects of a tissue-engineered sling in an animal model of stress urinary incontinence (SUI). MATERIALS AND METHODS Twenty female Sprague-Dawley rats were divided into four equal groups: a control group (C) had no intervention before the leak-point pressure (LPP) was measured; a denervated group (D) had bilateral proximal sciatic nerve transection (PSNT) and periurethral dissection with no sling placed; group S had concomitant bilateral PSNT and a suburethral sling of small intestinal submucosa (SIS) placed; and group (M) had concomitant bilateral PSNT with implantation of a tissue-engineered sling. The suburethral sling was placed via a transabdominal approach with the sling sutured to the pubic bone. Tissue-engineered slings were prepared with muscle-derived cells obtained via the pre-plate technique and subsequently seeded for 2 weeks on a SIS scaffold. Suburethral slings were implanted 2 weeks before LPP testing, using the vertical-tilt method. RESULTS Surgically placing a suburethral sling is feasible in the female rat, with few complications. LPPs from both sling groups (S and M) were not significantly different from untreated controls (C). The S, M and C groups all had significantly higher LPPs than group D. Importantly, no rat from either sling group (S and M) had signs of urinary retention. CONCLUSIONS Placing tissue-engineered slings in an animal model of SUI resulted in LPP values that were not significantly different from those in untreated control or SIS (S) groups. These data show that incorporating muscle stem cells into SIS slings does not adversely alter the advantageous mechanical properties of the SIS sling in a model of SUI, and provide the basis for future functional studies of tissue-engineered sling materials with long-term retention. [source] | |||||||||||||